Asthma and lower airway disease
A high-fat challenge increases airway inflammation and impairs bronchodilator recovery in asthma

https://doi.org/10.1016/j.jaci.2011.01.036Get rights and content

Background

Dietary fat activates systemic innate immune responses, but the effect on airway responses is unknown.

Objective

To examine effects of a high-fat versus low-fat meal on systemic and airway inflammation in asthma.

Methods

Nonobese subjects with asthma were randomized to consume a high-fat (n = 19; 48% [49 g] fat) or low-fat (n = 18; 15% [3 g] fat) meal. Fourteen obese patients with asthma and 21 healthy controls also consumed a high-fat meal. Another group of patients with asthma consumed a high-trans (n = 5; 5.2 g trans fat) or nontrans (n = 5, <0.3 g trans fat) fatty acid meal. Lung function was measured at baseline (prebronchodilator) and 2, 3, and 4 hours after bronchodilator. Airway inflammation was assessed by using induced sputum cell counts and Toll-like receptor 4 mRNA expression by real-time PCR. Systemic inflammation was measured by ELISA quantification of plasma TNF-α, high-sensitivity C-reactive protein, and IL-6 concentrations.

Results

In patients with asthma, at 4 hours postmeal, increases in sputum % neutrophils and Toll-like receptor 4 mRNA expression were higher and increases in FEV1/forced vital capacity (FVC) were lower in the high-fat versus low-fat groups. Changes in plasma fatty acids correlated with changes in sputum % neutrophils and were negatively associated with changes in % FEV1, % FVC, and FEV1/FVC. After the high-trans fatty acid meal, sputum % neutrophils were significantly higher than after the nontrans meal.

Conclusion

A high-fat meal augments neutrophilic airway inflammation, with the effect dependent on the type of fat consumed. A high-fat meal also suppresses bronchodilator recovery in asthma. Modifying dietary fat intake may be useful in asthma.

Section snippets

Study participants

Nonobese (body mass index [BMI] < 30 kg/m2; n = 37) and obese (BMI ≥ 30 kg/m2; n = 14) subjects older than 18 years with stable asthma were recruited. Before the study, subjects fasted for 12 hours and withheld short-acting and long-acting β-agonist medications. Exclusion criteria were current smoking (smoked within past 6 months), abnormal electrocardiogram at screening, pregnancy, diabetes mellitus, cardiac arrhythmia, angina, congestive heart failure, renal or hepatic failure, and systemic

Results

Compared with baseline, there was a significant increase in plasma levels of total fatty acids, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFA) at 4 hours after the high-fat challenge (Table I). The high-fat challenge led to a significantly greater increase in plasma levels of total fatty acids, SFAs, and MUFAs than the low-fat challenge (Table I).

There were no significant differences in age or sex of each of the groups (Table II). There

Discussion

This is the first study to investigate the direct effect of dietary fat on systemic and airway inflammation in asthma. We have demonstrated that in patients with asthma, consumption of a single high-fat meal leads to increased circulating fatty acid levels, and this corresponds with an increase in induced sputum % neutrophils and TLR4 mRNA expression in sputum cells. This fat-induced inflammation corresponds with attenuation of airway bronchodilator recovery, which correlates with the increase

References (47)

  • L. Zhao et al.

    Differential modulation of Nods signaling pathways by fatty acids in human colonic epithelial HCT116 cells

    J Biol Chem

    (2007)
  • F. Nappo et al.

    Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: role of fat and carbohydrate meals

    J Am Coll Cardiol

    (2002)
  • C. Bellido et al.

    Butter and walnuts, but not olive oil, elicit postprandial activation of nuclear transcription factor κB in peripheral blood mononuclear cells from healthy men

    Am J Clin Nutr

    (2004)
  • J.Y. Lee et al.

    Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4

    J Biol Chem

    (2001)
  • J.Y. Lee et al.

    Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1

    J Biol Chem

    (2004)
  • H. Shi et al.

    TLR4 links innate immunity and fatty acid-induced insulin resistance

    J Clin Invest

    (2006)
  • C. Patel et al.

    Prolonged reactive oxygen species generation and nuclear factor-κB activation after a high-fat, high-carbohydrate meal in the obese

    J Clin Endocrinol Metab

    (2007)
  • P. Blackburn et al.

    Postprandial variations of plasma inflammatory markers in abdominally obese men

    Obesity

    (2006)
  • R.H. Unger

    Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome

    Endocrinology

    (2003)
  • A.M. Cuevas et al.

    Diet and endothelial dysfunction

    Biol Res

    (2004)
  • F. Kim et al.

    Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity

    Circ Res

    (2007)
  • J.L. Simpson et al.

    Innate immune activation in neutrophilic asthma and bronchiectasis

    Thorax

    (2007)
  • C.L. Ordonez et al.

    Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma

    Am J Respir Crit Care Med

    (2000)
  • Cited by (0)

    Supported by a National Health and Medical Research Council of Australia Project Grant and a Hunter Medical Research Institute project grant sponsored by the Piggott family.

    Disclosure of potential conflict of interest: L. G. Wood has received honoraria from GlaxoSmithKline and has received research support from the National Health and Medical Research Council. M. L. Garg declares no conflicts of interest. P. G. Gibson has received honoraria from GlaxoSmithKline and Boehringer Ingelheim and has received research support from the National Health and Medical Research Council.

    View full text